Primary cutaneous amoebiasis is rare, and typically affects immunocompromised patients and presents with unique clinical and histopathologic changes. Untreated, the infection could progress to involve the central nervous system, which is almost universally fatal. We present a case of primary cutaneous acanthamoebiasis in a patient with chronic lymphocytic leukemia on acalabrutinib. Timely diagnosis and treatment resulted in complete resolution of lesions and a disease-free status at the 14-month follow-up. A 76-year-old man presented with a 2-month history of multiple, nonhealing, ulcerated, erythematous, painful, crusted nodules on his trunk, and upper and lower extremities. Two punch biopsies showed mixed inflammatory infiltrate with a histiocytic reaction and microabscesses extending into the deep dermis. Rare, unusual structures with cytoplasmic vacuolations and round nuclei were seen on repeated biopsies. Gomori methenamine silver delineated wrinkled double-walled cytoplasm of rare parasites, concerning for amoebic infection. Molecular workup (polymerase chain reaction) came back positive for Acanthamoeba castellanii. Initial treatment involved flucytosine and fluconazole, followed by fluconazole and miltefosine, but both were discontinued because of nausea and replaced with single-agent voriconazole. Acanthamoeba cutis poses unique diagnostic challenges in a setting of novel agents for chronic lymphocytic leukemia and may be underrecognized. With the expanding population of immunocompromised patients, rare cutaneous infections should enter the differential early on along with early consideration of molecular ancillary testing. The long-term immunomodulating properties of acalabrutinib remain to be elucidated.
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